Biomolecules such as nucleic acids and proteins have been increasingly exploited for applications in medical, chemical, agricultural, and food industries.  However, a major limitation in the applications of biomolecules is the existence of a functional gap between naturally occurring biomolecules and those required by specific practical settings.  Thus, how to close this functional gap has become a première intellectual and engineering challenge.  In this talk, I will discuss our recent work on the development of new biomolecular engineering tools and their applications.  Specifically, I will discuss: (1) developing estrogen receptor based genetic switches for human gene therapy; (2) engineering a novel phosphite-dehydrogenase based NAD(P)H cofactor regeneration system, and (3) designing new biosynthetic pathways for synthesis of thermally stable energetic compounds.